scholarly journals Identification of RRM2 as a Potential Biomarker for the Diagnosis and Prognosis of Rheumatoid Arthritis

2021 ◽  
Author(s):  
Wu Biao ◽  
Yufeng Chen ◽  
Junlong Zhong ◽  
Shuping Zhong ◽  
Bin Wang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Mononuclear Cells ◽  
Expression Profiles ◽  
Clinical Samples ◽  
Healthy Controls ◽  
Rna Seq ◽  
Hub Genes ◽  
Healthy Human ◽  
Bioinformatics Analyses ◽  
Potential Biomarker

Abstract Background: Rheumatoid arthritis (RA) is a common autoimmune disease that can occur at any age. If treatment is delayed, RA can seriously affect the patients’ quality of life. However, there is no diagnostic criteria for RA and the positive predictive value of the current biomarkers is moderate. Objective: to identify RA-associated susceptibility genes and explore their potential as a novel biomarker for diagnosis and evaluation of the prognosis of RA.Methods: Peripheral blood mononuclear cells (PBMCs) were collected from healthy human donors and RA patients. RNA-seq analyses were performed to identify the differentially expressed genes (DEGs) between RA and control samples. The PBMCs-mRNA in DEGs were further subjected to enrichment analysis. Furthermore, the hub genes and key modules associated with RA were screened by bioinformatics analyses. Then, the expression of hub genes in RA were assessed in mRNA expression profiles. Next, real time-quantitative PCR (RT-qPCR) analyses were performed to further confirm the expression of the hub genes from the PBMCs that collected from 47 patients with RA and 40 healthy controls. Finally, we evaluated the clinical characters for the candidate mRNAs.Results: RNA-seq analyses revealed the expression of 178 mRNAs from PBMCs were disregulated between the healthy controls and the RA patients. Bioinformatics analyses revealed 10 hub mRNAs. The top 3 significant functional modules screened from PPI network functionally were involved in DNA replication origin binding, chemokine activity, etc. After validating the 10 hub mRNAs in GSE93272 dataset and clinical samples, we identified 3 candidate mRNAs, including ASPM, DTL and RRM2. Among which, RRM2 showed great capacity in discriminating between remissive RA and active RA. Significant correlations were observed between DTL and IL-8, TNF-α, between RRM2 and CDAI, DAS-28, tender joints and swollen joints, respectively. The AUC values of ASPM, DTL and RRM2 were 0.654, 0.995 and 0.990, respectively.Conclusion: We successfully identified multiple candidate mRNAs associated with RA. RRM2 showed high diagnosis efficiency with the AUC of 0.990 (sensitivity=100%, specificity=97.5%). And RRM2 severed as an additional biomarker for evaluating disease activity. The findings provided a novel candidate biomarker for diagnosis and evaluation of the prognosis of RA.

scholarly journals Using protein microarray reveals clinical correlation between self-perception of patient and the apoptosis-related proteins in rheumatoid arthritis

2020 ◽  
Author(s):  
Jian-ting Wen ◽  
Jian Liu ◽  
Hui Jiang ◽  
Lei Wan ◽  
Ling Xin ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Mononuclear Cells ◽  
Expression Profiles ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Controls ◽  
Self Perception ◽  
Roc Curve Analysis ◽  
Peripheral Blood Mononuclear ◽  
Related Proteins ◽  
Potential Biomarkers

Abstract Background: The most severe effects of rheumatoid arthritis (RA) are loss of physical function, which may have a significant impact on self-perception of patient (SPP). However, the inherent relationship between SPP and the key proteins is not clear. The aim of this study was to get an insight into SPP of RA in connection with the the apoptosis-related proteins. Methods: We set out to investigate changes of the apoptosis-related proteins expression in the peripheral blood mononuclear cells (PBMCs) of RA. Additionally, we aimed to correlate the apoptosis-related proteins expression profiles with SPP and clinical indexes. To this end, we employed antibody microarrays of the the apoptosis-related proteins in PBMCs from four RA patients and seven healthy controls. We used bioinformatics to screen several the apoptosis-related proteins. To validate key protein candidates, we performed Enzyme linked immunosorbent assay (ELISA) on 30 RA patients and 30 healthy controls. Results: We found the expression of ten the apoptosis-related proteins (caspase3, CD40, SMAC, HSP27, HTRA, IGFBP-1, IGFBP-6, sTNF-R1, sTNF-R2, TRAILR-3) were significantly altered in PBMCs of RA patients. Receiver operating characteristic (ROC) curve analysis suggested that these ten the apoptosis-related proteins are potential biomarkers of RA. Spearman Correlation analysis and Logistic-regression analysis revealed that the 10 selected the apoptosis-related proteins correlated with SPP and clinical indexes. Conclusion: Therefore, we highlight some the apoptosis-related proteins may serve as potential biomarkers in prediction of SPP for RA patients, although the underlying mechanisms need to be further explored.

scholarly journals RNA-Seq profiling revealed PBMC RNA as potential biomarker for hepatocellular carcinoma

2020 ◽  
Author(s):  
Zhiyi Han ◽  
Wenxing Feng ◽  
Rui Hu ◽  
Qinyu Ge ◽  
Wenfeng Ma ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Mononuclear Cells ◽  
Healthy Controls ◽  
Rna Seq ◽  
Sequencing Data ◽  
Peripheral Blood Mononuclear ◽  
Qrt Pcr ◽  
Potential Biomarker ◽  
Incidence And Mortality ◽  
Differential Expressed Gene

Abstract Background Hepatocellular carcinoma is one of the most common malignancies with extremely high incidence and mortality rates. Although there have been many studies focus on biomarkers study, few have been reported on PBMC RNA profiles of hepatocellular carcinoma. Methods In this study, we attempted to profile the expression of Peripheral Blood Mononuclear Cells (PBMCs) RNA by using RNA-seq technology and compared the transcriptome between hepatocellular carcinoma patients and the healthy controls. 17 patients and 17 healthy controls involved in this study, PBMCs RNA were sequenced. The sequencing data were analyzed with bioinformatics tools and qRT-PCR was used for selected differential expressed gene validation. Results It is showed that 1578 dysregulated genes found including 1334 upregulated genes and 244 downregulated genes. GO enrichment and KEGG analysis denoted most of the differential expressed genes (DEGs) involved in immune response are closely related to hepatocellular carcinoma. Expression of the 6 selected genes (DEGs, SELENBP1, SLC4A1, SLC26A8, HSPA8P4, CALM1, and RPL7p24) were confirmed by qRT-PCR, and higher sensitivity and specificity obtained by ROC analysis of the 6 genes. CALM1 was found gradually decreasing along with the tumor enlarged. Conclusions It is suggested potential biomarker for diagnosis, classification and therapeutic target of hepatocellular carcinomas. This study provided new visions into development of liver cancer and potential efficient clinical diagnosis in the future.

scholarly journals RNA-Seq Profiling Revealed PBMC RNA as Potential Biomarker for Hepatocellular Carcinoma

2021 ◽  
Author(s):  
Zhiyi Han ◽  
Wenxing Feng ◽  
Rui Hu ◽  
Qinyu Ge ◽  
Wenfeng Ma ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Mononuclear Cells ◽  
Malignant Tumors ◽  
High Morbidity ◽  
Healthy Controls ◽  
Rna Seq ◽  
Sequencing Data ◽  
Qrt Pcr ◽  
Potential Biomarker ◽  
Response Expression

Abstract Background: Hepatocellular carcinoma with extremely high morbidity and mortality is one of the most common malignant tumors. Although many existing studies focus on the study of its biomarkers, little information has been released on the PBMC RNA profile of hepatocellular carcinoma. Methods: We tried to make a profile throughout this analysis with the expression of Peripheral Blood Mononuclear Cells (PBMCs) RNA by using RNA-seq technology and compared the transcriptome between hepatocellular carcinoma patients and the healthy controls. 17 patients and 17 healthy controls involved in this study, PBMCs RNA were sequenced. The sequencing data were analyzed with bioinformatics tools and qRT-PCR was used for selected differential expressed gene validation. Results: It is showed that 1578 dysregulated genes found including 1334 upregulated genes and 244 downregulated genes. GO enrichment and KEGG studies showed that hepatocellular carcinoma is a closely linked source of the most differentially expressed genes (DEGs), implicated in the immune response. Expression of the 6 selected genes (SELENBP1, SLC4A1, SLC26A8, HSPA8P4, CALM1, and RPL7p24) were confirmed by qRT-PCR, and higher sensitivity and specificity obtained by ROC analysis of the 6 genes. CALM1 was found gradually decreasing along with the tumor enlarged. Conclusions: It is suggested potential biomarker for diagnosis of hepatocellular carcinomas. This study provided new perspectives for liver cancer development and possible future successful clinical diagnosis.

scholarly journals Integrated analysis of competing endogenous RNA networks in peripheral blood mononuclear cells of systemic lupus erythematosus

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Wencong Song ◽  
Jie Qiu ◽  
Lianghong Yin ◽  
Xiaoping Hong ◽  
Weier Dai ◽  
...  
Keyword(s):  
Differential Expression ◽  
Lupus Erythematosus ◽  
Mononuclear Cells ◽  
Expression Profiles ◽  
Signalling Pathways ◽  
Rna Seq ◽  
Systemic Lupus ◽  
Hub Genes ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells

Abstract Background Systemic lupus erythematosus (SLE) is an autoimmune disease with a complicated pathogenesis, and its aetiology has not been clearly unveiled. The lack of effective diagnosis and treatment methods makes it necessary to explore the molecular mechanism of SLE. We aimed to identify some critical signalling pathways and key competing endogenous RNAs (ceRNAs) underlying the molecular mechanism of SLE and to map out the systematic signalling networks by integrating the data on different kinds of RNAs. Methods Peripheral blood mononuclear cells (PBMCs) were collected from both SLE patients and healthy subjects, RNA was extracted from the PBMCs, and RNA libraries including ribosomal RNA-depleted strand-specific libraries and small RNA libraries were built for deep RNA sequencing (RNA-seq). RNA-seq yielded differential expression profiles of lncRNAs/circRNAs/miRNAs/mRNAs related to SLE. The DAVID database (v. 6.8) was employed for Gene Ontology (GO) and KEGG pathway analysis. ceRNA networks (circRNA/lncRNA-miRNA-mRNA) were constructed and visualized using Cytoscape software (v. 3.5.0). The TargetScan and miRanda databases were used to predict target relationships in ceRNA networks. qRT-PCR was used to verify our data. Results Differential expression of ceRNAs related to SLE was detected in SLE patients’ PBMCs: 644 mRNAs (384 upregulated, 260 downregulated), 326 miRNAs (223 upregulated, 103 downregulated), 221 lncRNAs (79 upregulated, 142 downregulated), and 31 circRNAs (21 upregulated, 10 downregulated). We drew ceRNA signalling networks made up of the differentially expressed mRNAs/miRNAs/lncRNAs/circRNAs mentioned above, and the hub genes included IRF5, IFNAR2, TLR7, IRAK4, STAT1, STAT2, C2, and Tyk2. These hub genes were involved in ceRNA signalling pathways, such as the IL-17 signalling pathway and type I interferon signalling pathway. Conclusions We explored the differential expression profiles of various kinds of ceRNAs and integrated signalling networks constructed by ceRNAs. Our findings offer new insights into the pathogenesis of SLE and hint at therapeutic strategies.

scholarly journals Dysregulations of MicroRNA and Gene Expression in Chronic Venous Disease

2020 ◽  
Vol 9 (5) ◽  
pp. 1251 ◽  
Author(s):  
Daniel P. Zalewski ◽  
Karol P. Ruszel ◽  
Andrzej Stępniewski ◽  
Dariusz Gałkowski ◽  
Jacek Bogucki ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mononuclear Cells ◽  
Varicose Veins ◽  
Expression Profiles ◽  
Lower Limbs ◽  
Chronic Venous Disease ◽  
Venous Disease ◽  
Operating Characteristics ◽  
Potential Biomarker ◽  
Pathologic Features

Chronic venous disease (CVD) is a vascular disease of lower limbs with high prevalence worldwide. Pathologic features include varicose veins, venous valves dysfunction and skin ulceration resulting from dysfunction of cell proliferation, apoptosis and angiogenesis. These processes are partly regulated by microRNA (miRNA)-dependent modulation of gene expression, pointing to miRNA as a potentially important target in diagnosis and therapy of CVD progression. The aim of the study was to analyze alterations of miRNA and gene expression in CVD, as well as to identify miRNA-mediated changes in gene expression and their potential link to CVD development. Using next generation sequencing, miRNA and gene expression profiles in peripheral blood mononuclear cells of subjects with CVD in relation to healthy controls were studied. Thirty-one miRNAs and 62 genes were recognized as potential biomarkers of CVD using DESeq2, Uninformative Variable Elimination by Partial Least Squares (UVE-PLS) and ROC (Receiver Operating Characteristics) methods. Regulatory interactions between potential biomarker miRNAs and genes were projected. Functional analysis of microRNA-regulated genes revealed terms closely related to cardiovascular diseases and risk factors. The study shed new light on miRNA-dependent regulatory mechanisms involved in the pathology of CVD. MicroRNAs and genes proposed as CVD biomarkers may be used to develop new diagnostic and therapeutic methods.

scholarly journals COVID-19 Severity Potentially Modulated by Cardiovascular-Disease-Associated Immune Dysregulation

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1018
Author(s):  
Abby C. Lee ◽  
Grant Castaneda ◽  
Wei Tse Li ◽  
Chengyu Chen ◽  
Neil Shende ◽  
...  
Keyword(s):  
Rna Sequencing ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Expression Profiles ◽  
Immune Dysregulation ◽  
Left Ventricular ◽  
Recurrent Event ◽  
Healthy Controls ◽  
Sequencing Data ◽  
Peripheral Blood Mononuclear

Patients with underlying cardiovascular conditions are particularly vulnerable to severe COVID-19. In this project, we aimed to characterize similarities in dysregulated immune pathways between COVID-19 patients and patients with cardiomyopathy, venous thromboembolism (VTE), or coronary artery disease (CAD). We hypothesized that these similarly dysregulated pathways may be critical to how cardiovascular diseases (CVDs) exacerbate COVID-19. To evaluate immune dysregulation in different diseases, we used four separate datasets, including RNA-sequencing data from human left ventricular cardiac muscle samples of patients with dilated or ischemic cardiomyopathy and healthy controls; RNA-sequencing data of whole blood samples from patients with single or recurrent event VTE and healthy controls; RNA-sequencing data of human peripheral blood mononuclear cells (PBMCs) from patients with and without obstructive CAD; and RNA-sequencing data of platelets from COVID-19 subjects and healthy controls. We found similar immune dysregulation profiles between patients with CVDs and COVID-19 patients. Interestingly, cardiomyopathy patients display the most similar immune landscape to COVID-19 patients. Additionally, COVID-19 patients experience greater upregulation of cytokine- and inflammasome-related genes than patients with CVDs. In all, patients with CVDs have a significant overlap of cytokine- and inflammasome-related gene expression profiles with that of COVID-19 patients, possibly explaining their greater vulnerability to severe COVID-19.

scholarly journals Peripheral Blood Gene Expression and IgG Glycosylation Profiles as Markers of Tocilizumab Treatment in Rheumatoid Arthritis

2012 ◽  
Vol 39 (5) ◽  
pp. 916-928 ◽  
Author(s):  
BERTALAN MESKO ◽  
SZILARD POLISKA ◽  
SZILVIA SZAMOSI ◽  
ZOLTAN SZEKANECZ ◽  
JANOS PODANI ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Gene Expression ◽  
Peripheral Blood ◽  
Multiple Testing ◽  
Mononuclear Cells ◽  
Expression Profiles ◽  
Quantitative Polymerase Chain Reaction ◽  
Response To Treatment ◽  
Peripheral Blood Mononuclear ◽  
Gene Sets

Objective.Tocilizumab, a humanized anti-interleukin-6 receptor monoclonal antibody, has recently been approved as a biological therapy for rheumatoid arthritis (RA) and other diseases. It is not known if there are characteristic changes in gene expression and immunoglobulin G glycosylation during therapy or in response to treatment.Methods.Global gene expression profiles from peripheral blood mononuclear cells of 13 patients with RA and active disease at Week 0 (baseline) and Week 4 following treatment were obtained together with clinical measures, serum cytokine levels using ELISA, and the degree of galactosylation of the IgG N-glycan chains. Gene sets separating responders and nonresponders were tested using canonical variates analysis. This approach also revealed important gene groups and pathways that differentiate responders from nonresponders.Results.Fifty-nine genes showed significant differences between baseline and Week 4 and thus correlated with treatment. Significantly, 4 genes determined responders after correction for multiple testing. Ten of the 12 genes with the most significant changes were validated using real-time quantitative polymerase chain reaction. An increase in the terminal galactose content of N-linked glycans of IgG was observed in responders versus nonresponders, as well as in treated samples versus samples obtained at baseline.Conclusion.As a preliminary report, gene expression changes as a result of tocilizumab therapy in RA were examined, and gene sets discriminating between responders and nonresponders were found and validated. A significant increase in the degree of galactosylation of IgG N-glycans in patients with RA treated with tocilizumab was documented.

scholarly journals Therapeutic Potential of a Novel Bifidobacterium Identified Through Microbiome Profiling of RA Patients With Different RF Levels

2021 ◽  
Vol 12 ◽  
Author(s):  
Yunju Jeong ◽  
JooYeon Jhun ◽  
Seon-Yeong Lee ◽  
Hyun Sik Na ◽  
JeongWon Choi ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Relative Abundance ◽  
Th17 Cells ◽  
Mononuclear Cells ◽  
Therapeutic Potential ◽  
Human Peripheral Blood ◽  
Cartilage Damage ◽  
Therapeutic Effects ◽  
Bioinformatics Analyses ◽  
Proinflammatory Mediators

The potential therapeutic effects of probiotic bacteria in rheumatoid arthritis (RA) remain controversial. Thus, this study aimed to discover potential therapeutic bacteria based on the relationship between the gut microbiome and rheumatoid factor (RF) in RA. Bacterial genomic DNA was extracted from the fecal samples of 93 RA patients and 16 healthy subjects. Microbiota profiling was conducted through 16S rRNA sequencing and bioinformatics analyses. The effects of Bifidobacterium strains on human peripheral blood mononuclear cells and collagen-induced arthritis (CIA) mice were assessed. Significant differences in gut microbiota composition were observed in patients with different RF levels. The relative abundance of Bifidobacterium and Collinsella was lower in RF-high than in RF-low and RF-negative RA patients, while the relative abundance of Clostridium of Ruminococcaceae family was higher in RF-high than in RF-low and RF-negative patients. Among 10 differentially abundant Bifidobacterium, B. longum RAPO exhibited the strongest ability to inhibit IL-17 secretion. Oral administration of B. longum RAPO in CIA mice, obese CIA, and humanized avatar model significantly reduced RA incidence, arthritis score, inflammation, bone damage, cartilage damage, Th17 cells, and inflammatory cytokine secretion. Additionally, B. longum RAPO significantly inhibited Th17 cells and Th17-related genes—IL-17A, IRF4, RORC, IL-21, and IL-23R—in the PBMCs of rheumatoid arthritis patients. Our findings suggest that B. longum RAPO may alleviate RA by inhibiting the production of IL-17 and other proinflammatory mediators. The safety and efficacy of B. longum RAPO in patients with RA and other autoimmune disorders merit further investigation.

scholarly journals Differential Expression Profiles of the Transcriptome and miRNA Interactome in Synovial Fibroblasts of Rheumatoid Arthritis Revealed by Next Generation Sequencing

Diagnostics ◽  
2019 ◽  
Vol 9 (3) ◽  
pp. 98
Author(s):  
Chia-Chun Tseng ◽  
Ling-Yu Wu ◽  
Wen-Chan Tsai ◽  
Tsan-Teng Ou ◽  
Cheng-Chin Wu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Differential Expression ◽  
Regulatory Network ◽  
Functional Annotation ◽  
Interaction Analysis ◽  
Expression Profiles ◽  
Synovial Fibroblasts ◽  
Rna Seq ◽  
Network Mapping ◽  
Generation Sequencing

Using next-generation sequencing to decipher the molecular mechanisms underlying aberrant rheumatoid arthritis synovial fibroblasts (RASF) activation, we performed transcriptome-wide RNA-seq and small RNA-seq on synovial fibroblasts from rheumatoid arthritis (RA) subject and normal donor. Differential expression of mRNA and miRNA was integrated with interaction analysis, functional annotation, regulatory network mapping and experimentally verified miRNA–target interaction data, further validated with microarray expression profiles. In this study, 3049 upregulated mRNA and 3552 downregulated mRNA, together with 50 upregulated miRNA and 35 downregulated miRNA in RASF were identified. Interaction analysis highlighted contribution of miRNA to altered transcriptome. Functional annotation revealed metabolic deregulation and oncogenic signatures of RASF. Regulatory network mapping identified downregulated FOXO1 as master transcription factor resulting in altered transcriptome of RASF. Differential expression in three miRNA and corresponding targets (hsa-miR-31-5p:WASF3, hsa-miR-132-3p:RB1, hsa-miR-29c-3p:COL1A1) were also validated. The interactions of these three miRNA–target genes were experimentally validated with past literature. Our transcriptomic and miRNA interactomic investigation identified gene signatures associated with RASF and revealed the involvement of transcription factors and miRNA in an altered transcriptome. These findings help facilitate our understanding of RA with the hope of serving as a springboard for further discoveries relating to the disease.

Sign in / Sign up

Export Citation Format

Share Document